Single conduit multi-electrode cardiac pacemaker and methods of using thereof

ABSTRACT

A device and method for providing cardiac pacing of triangle of Koch and bundle of His zones by multiple electrodes inserted using in a single conduit are provided. The method includes providing a single conduit with multiple electrodes, positioning electrodes in the target zone of a heart, selecting acceptable electrodes as active based on a predetermined criteria and providing cardiac stimulation for multiple chambers of the heart from a single location.

BACKGROUND OF THE INVENTION

The present invention relates generally to cardiac pacing. Moreparticularly, the invention describes multiple embodiments of asingle-conduit multi-electrode cardiac pacemaker configured forstimulating the bundle of His and surrounding areas for pacing theentire heart and methods of using thereof.

In a healthy heart, a heartbeat originates in a specialized cardiacconduction system and spreads via this system to all parts of themyocardium. The structures that make up the conduction system are thesinoatrial node (SA node), the internodal atrial pathways, theatrioventricular node (AV node), the bundle of His and its branches, andthe Purkinje system. Activation spreads quickly across the atria to theAV node, which then delays the wave of excitation. The delay enables theatria to contract before the ventricles contract. After the activationis delayed by, and leaves, the AV node, it enters and excites the bundleof His. This excitation of the bundle of His spreads in a precisepattern to the ventricles through the ventricular conduction systemcomposed of Purkinje fibers. Excitation spreading through this systemactivates each ventricular cell at a precise time to produce acoordinated ventricular contraction. These events are seen generally asa normal QRS signal composed of group of waveforms on electrocardiogram(ECG) representing ventricular depolarization.

For various reasons, this process of normal propagation of theelectrical excitation wave throughout the heart may be disrupted leadingto a variety of conduction abnormalities and subsequently to abnormalheart contractility. Many such abnormalities may be seen on the ECGsignal and can be detected as distorted or absent P-wave or QRS signal.Such abnormalities may be treated by using an implantable cardiacpacemaker configured to generate artificial pacing signals when naturalexcitation/conduction is disrupted or absent altogether.

Traditional pacemakers include typically 2 or 3 individual wires orleads that extend separately to different chambers of the heart andprovide electrical stimulation from different locations within theheart. In modern pacemakers, each individual electrode may be activatedin a unipolar mode using the body of the implanted pacemaker itself forexample as a ground electrode. More recently, a bipolar mode ofelectrode activation is used in which each individual lead is equippedwith a second ring electrode (usually serving in an anode capacity)which may be spaced apart from the negative (cathode) electrode. Thering electrode may or may not be in touch with the cardiac tissue butstill supports the activation of the main electrode via conductionthrough blood in the vicinity thereof.

Recent experience with cardiac pacing indicates that traditional pacingsites may not be ideal for a good number of patients. Particularly, thisis the case for right ventricular pacing, which may result in decline inheart function in some patients due to asynchronous cardiac contraction.Therefore, new direction in pacing is needed to avoid asynchronouscardiac contraction. This was attempted by pacing directly into thenatural conduction system of the heart and more specifically—stimulatingthe bundle of His. This area is located right in the center of the heartin close proximity to atrial and ventricular tissue—and therefore mayallow stimulation of one or multiple chambers of the heart fromessentially the same location.

Permanent His bundle pacing (PHBP) has a potential to be used fortreatment of at least some of the conduction abnormalities such as forexample intra- and infra-hisian block including a complete heart blockand left bundle branch block (Barba-Pichardo R, Moriña-Vázquez P,Venegas-Gamero J, Maroto-Monserrat F, Cid-Cumplido M, Herrera-CarranzaM. [Permanent His-bundle pacing in patients with infra-Hisianatrioventricular block]. Rev EspCardiol. 2006; 59(6):553-558; LustgartenD L, Calame S, Crespo E M, Calame J, Lobel R, Spector P S. Electricalresynchronization induced by direct His-bundle pacing. Heart Rhythm.2010; 7(1):15-21; Kronborg M B, Mortensen P T, Gerdes J C, Jensen H K,Nielsen J C. His and para-His pacing in AV block: feasibility andelectrocardiographic findings. J Interv Card Electrophysiol. 2011;31(3):255-262; Sharma P S, Vijayaraman P. His Bundle Pacing OrBiventricular Pacing For Cardiac Resynchronization Therapy In HeartFailure: Discovering New Methods For An Old Problem. J Atr Fibrillation.2016; 9(4):1501; Herweg B, Gerczuk P Z, Sofi A, Vijayaraman P, Barold SS. Permanent His Bundle Pacing in Intra-Hisian Conduction Block:Mechanistic Insights. J Electrocardiol. 2017; 50(6):933-936.).

In patients undergoing pacemaker implantation, PHBP was found to beassociated with reduction in death or heart failure hospitalizationduring long-term follow-up compared to a more conventional rightventricular pacing. Bundle of His pacing was also associated with higherrates of lead revisions and generator change. (Vijayaraman P,Naperkowski A, Subzposh F A, et al. Permanent His-bundle pacing:Long-term lead performance and clinical outcomes. Heart Rhythm.2018:15(5); 696-702). In patients with heart failure and left bundlebranch block, PHBP, as an alternative means to achieve cardiacresynchronization, has been shown to be feasible (Lustgarten D L, CrespoE M, Arkhipova-Jenkins I, et al. His-bundle pacing versus biventricularpacing in cardiac resynchronization therapy patients: A crossover designcomparison. Heart Rhythm. 2015; 12(7):1548-1557) and possibly beneficialcompared to biventricular pacing (Sharma P S, Dandamudi G, Herweg B, etal. Permanent His-bundle pacing as an alternative to biventricularpacing for cardiac resynchronization therapy: A multicenter experience.Heart Rhythm. 2018; 15(3):413-420).

Despite the recent technological progress with the design ofelectrophysiology (EP) mapping catheters and pacing leads, their abilityto reliably reach the target area at and surrounding the bundle of Hisin patients with broad anatomical variations is very limited.

Currently, successful placement of the pacing lead to a bundle of His isonly achieved in approximately 80% of the cases (Vijayaraman P,Dandamudi G, Zanon F, et al. Permanent His bundle pacing:Recommendations from a Multicenter His Bundle Pacing CollaborativeWorking Group for standardization of definitions, implant measurements,and follow-up. Heart Rhythm. 2018; 15(3):460-468). This is frequentlydue to the inability to attach the electrode to a successfullyidentified target site with a reasonable capture threshold. To this day,the area to deploy the pacing electrode is identified by traditionalmethods of a multipolar electrode catheter used as a rough guide in apoint-by-point electrogram mapping. Additionally, determination of thebundle of His capture is not always clear or easy to determineclinically.

Conventionally, a single electrode is used for probing and searching forthe best position for implantation. Such probing procedure uses atemporary attachment of the electrode to the endocardial surface of thecardiac tissue followed by successive cardiac stimulation starting athigher voltages and subsequently reducing the voltage until the responseof the cardiac tissue is no longer observed on the ECG—so as todetermine a threshold for the lowest effective stimulation voltage. Ifthe desired ECG response cannot be achieved at all or can be achievedonly at high voltages, the electrode is disconnected from the tissue andmoved to another location where the process is repeated again. As morethan one cardiac chamber stimulation is frequently desired, this processmay be time consuming and may involve large number of fluoroscopyimages—leading to increased radiation exposure for both the patient andthe physician.

The lead placement therefore is dependent on a point-by-point mappingand pacing using a trial-and-error methodology. The need thereforeexists for better pacing tools and pacing leads to achieve a more rapidand effective permanent cardiac pacing. The need also exists to resolvea guidance problem of the pacing leads and achieve a reproduciblenavigation to predetermined capture sites—so as to improve theoperator's confidence, expedite the process of lead implantation andreduce radiation exposure due to excessive fluoroscopy imaging.

BRIEF SUMMARY OF THE INVENTION

Accordingly, it is an object of the present invention to overcome theseand other drawbacks of the prior art by providing a novel single conduitcardiac pacemaker configured for electrical evaluation and stimulationof the bundle of His and surrounding areas including the atrium.

It is another object of the present invention to provide a singleconduit cardiac pacemaker configured for reliable and deterministicimplantation in a broad range of patients with a variety of anatomicalvariations and abnormalities in electrical conduction of the cardiactissue.

A further object of the present invention is to provide a single conduitcardiac pacemaker and methods of using thereof allowing to rapidlyidentify best stimulation sites after implantation and to providecardiac pacing without a need to implant multiple individual electrodes.

In embodiments, the novel single conduit multi-electrode pacemakercomprises a single elongated insulated conduit housing a plurality ofelectrical conductors operably connected to a plurality of respectiveindividual electrodes at the distal end of the conduit. Individualelectrodes may be configured to be retained near the center of theconduit while constrained by a surrounding sheath. Retraction of thesheath allows the electrode to spread out radially away from the centerso as to allow simultaneous implantation into the target area of thecardiac tissue. As a result, a plurality of spaced apart electrodes maybe positioned in the cardiac tissue via a single implantation procedure.A central tissue attachment spring may also be provided to secure theconduit and all the individual electrodes in place. Individual positionof the electrodes may be selected to reliably cover the target area ofthe cardiac tissue such as the bundle of His with at least some of theelectrodes located in and around this selected target area which mayinclude the atrial tissue.

In other embodiments, following the positioning of the plurality ofelectrodes in and around the target area of the cardiac tissue,individual interrogation of these electrodes may be conducted with theaim of identifying desired electrodes located directly at the targetsite. Those electrodes that do not provide desired ECG response duringtest stimulation may be abandoned. If more than one electrode is foundto provide desired stimulation behavior, additional selection withinthis group may be conducted to identify one or more electrodes with thelowest threshold for effective cardiac stimulation.

In further embodiments, a method of providing cardiac pacing includesthe steps of providing a flexible single conduit housing a plurality ofindividual wires extending therethrough and terminating with a pluralityof corresponding individual electrodes located at the distal end of theconduit; advancing the single conduit to position a distal end thereofnear a cardiac tissue target area while the plurality of individualelectrodes are held in a collapsed position next to a center of thedistal end of the single conduit; expanding the plurality of individualelectrodes to an expanded position forming a predetermined expandedpattern of the individual electrodes about and away from the center ofthe distal end of the single conduit; advancing the single conduit toimplant the individual electrodes into the cardiac tissue target area;interrogating the plurality of individual electrodes to determine asubset of the individual electrodes meeting a predetermined acceptancecriteria; and initiating cardiac pacing using at least some ofindividual electrodes of the subset of individual electrodes meeting thepredetermined acceptance criteria, these at least some individualelectrode connected to a pacemaker.

Permanent pacing may then be initiated with an implantable pacemakerusing a subset of the plurality of electrodes that are best matched todesired cardiac pacing outcome.

BRIEF DESCRIPTION OF THE DRAWINGS

Subject matter is particularly pointed out and distinctly claimed in theconcluding portion of the specification. The foregoing and otherfeatures of the present disclosure will become more fully apparent fromthe following description and appended claims, taken in conjunction withthe accompanying drawings. Understanding that these drawings depict onlyseveral embodiments in accordance with the disclosure and are,therefore, not to be considered limiting of its scope, the disclosurewill be described with additional specificity and detail through use ofthe accompanying drawings, in which:

FIG. 1 is a general cross-sectional view of a heart with implantedmultiple electrodes into a target zone.

FIG. 2 is a schematic view of a close-up portion of the heart of FIG. 1including the triangle of Koch and bundle of His as the target zone.

FIGS. 3A, 3B, and 3C are perspective views of a tip of a conduit withmultiple electrodes according to the first embodiment of the invention.

FIGS. 4A, 4B, and 4C are perspective views of a tip of a conduit withmultiple electrodes according to the second embodiment of the invention.

FIGS. 5A and 5B are perspective views of a tip of a conduit withmultiple electrodes according to the third embodiment of the invention.

FIGS. 6A and 6B are perspective views of a tip of a conduit withmultiple electrodes according to the fourth embodiment of the invention.

FIG. 7 is a view of an implantable pacemaker assembly with multipleelectrodes according to the fifth embodiment of the present invention.

FIG. 8 is a schematic diagram of a cardiac pacemaker with a singleconduit combining multiple electrodes therein.

FIG. 9 is a block diagram illustrating the sequence of the stepsaccording to one method of the invention.

FIG. 10 illustrates measurement of HV interval with intracardiacelectrogram recording.

FIG. 11 illustrates selective stimulation of the His bundle with theprototype electrode in an animal heart.

FIG. 12 illustrates stimulation of ventricular myocardium by bothselective and nonselective His bundle capture with the prototypeelectrode in an animal heart.

FIG. 13 illustrates stimulation of atrial myocardium by the prototypeelectrode implanted into the triangle of Koch of an animal heart fromthe same position where the His bundle capture was obtained fromdifferent electrode pairs of the prototype.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS OF THE INVENTION

The following description sets forth various examples along withspecific details to provide a thorough understanding of claimed subjectmatter. It will be understood by those skilled in the art, however, thatclaimed subject matter may be practiced without one or more of thespecific details disclosed herein. Further, in some circumstances,well-known methods, procedures, systems, components and/or circuits havenot been described in detail in order to avoid unnecessarily obscuringclaimed subject matter. In the following detailed description, referenceis made to the accompanying drawings, which form a part hereof. In thedrawings, similar symbols typically identify similar components, unlesscontext dictates otherwise. The illustrative embodiments described inthe detailed description, drawings, and claims are not meant to belimiting. Other embodiments may be utilized, and other changes may bemade, without departing from the spirit or scope of the subject matterpresented here. It will be readily understood that the aspects of thepresent disclosure, as generally described herein, and illustrated inthe figures, can be arranged, substituted, combined, and designed in awide variety of different configurations, all of which are explicitlycontemplated and make part of this disclosure.

The present invention describes a single cardiac pacing conduit with aplurality of individual electrodes located at the distal end thereof.Initially, individual electrodes are located in a compressed state nextto the center of the conduit—so as to facilitate easy insertion andadvancement to the implantation site. While in the vicinity of thedesired implantation site, individual electrodes are expanded away fromthe center so as to form a plurality of electrodes configured to coverthe target area of the cardiac tissue. The conduit is then advancedfurther and all electrodes are implanted into the cardiac tissue at thedesired site. Location of individual electrodes may be selected toprovide adequate coverage of the target area and surrounding tissues sothat at least a subset of electrodes may be useful for subsequentcardiac pacing.

Once implantation of individual electrodes is accomplished (withoptional temporary or permanent tissue attachment to secure theelectrodes in place), individual or group interrogation of theelectrodes may commence. To evaluate individual electrodes, oneelectrode at a time may be activated in a unipolar or bi-polar mode withvarious levels of pacing voltage so as to determine whether its locationand performance is adequate for desired cardiac pacing purposes.Evaluation of all electrodes may be conducted using one electrode at atime or pairing electrodes with each other. As a result, preferredsubset of electrodes may be identified so as to determine the bestindividual electrodes or pairs of electrodes suitable for subsequentpacing purposes with the lowest effective voltage thresholds.

In embodiments, covering the bundle of His and triangle of Koch as wellas surrounding areas of cardiac tissues may result if identifyingelectrodes suitable for atrial pacing, selective bundle of His pacing ormixed pacing. Depending on the nature of cardiac abnormalities, a finalselection of electrodes may be conducted aimed at identifying the bestelectrodes located at the proper target area for each individualpatient.

In situations when no electrodes are found to be suitable for subsequentcardiac pacing, repositioning and re-implantation of the plurality ofelectrodes may be conducted so as to attempt to relocate the pluralityof electrodes in another position so as to allow another attempt to findone or more electrodes suitable for permanent cardiac pacing. Remainingelectrodes may be abandoned and not used for cardiac pacing followingsuch interrogation procedure. These remaining electrodes may remainpassive but can be optionally re-activated in the future if the cardiacdisease progresses and a different mode of pacing is needed for thepatient later in life. Another reason to leave passive electrodes inplace is to allow optional activation thereof in case of lead fractureor another malfunction of the initially selected electrodes. Havingother electrodes suitable for cardiac pacing may prevent immediatecomplications when switching to their use is done automatically by asuitable cardiac pacemaker operably connected to and programmed toperform such switch in this case. A further yet advantage of providingadditional electrodes is to avoid a surgical intervention to replace theentire conduit when one of the electrodes experienced a malfunction.

Specific embodiments of the present invention are now described ingreater detail.

Referring to FIG. 1, a human heart 1 is illustrated in a general waywith implanted therein a conduit of the invention 16 having multipleelectrodes 2 extending from a distal end thereof and into a target zonein the heart. Seen in the drawing are the following elements and heartstructures: distal electrodes 2 are extending from the distal tip of theconduit 16 into the target zone, which includes bundle of His 3.Bachmann's bundle 4 is seen as a conduction structure. Also shown arethe left atrium 5, left ventricle 6, left conduction bundle (or leftbundle branch) 7, descending aorta 8, inferior vena cava 9, rightconduction bundle (or right bundle branch) 10, right ventricle 11,atrioventricular node 12, right atrium 13, sinoatrial node 14, and asuperior vena cava 15. As with other pacing leads, a pacing conduit 16of the invention may be minimally invasively delivered through thesuperior vena cava 15, aorta 17, or left pulmonary artery 18.

FIG. 2 shows a schematic view of a portion of the heart of FIG. 1including the triangle of Koch 22 and bundle of His 3 that together andalong with surrounding atrial tissues may be contemplated as the targetarea 21 suitable for implantation of a plurality of pacing electrodes 2.The target area 21 may be accessed through the right atrium 13. To allowdistinct pictorial identification of the proper location of the targetarea 21, the following heart anatomical and functional structures aredepicted in FIG. 2: left bundle branch 24, right bundle branch 25,tricuspid valve 26, coronary sinus ostium 27, inferior vena cava 28,tendon of Todaro 29, and fossa ovalis 30. The penetrating bundle of His3 is a structure consisting of specialized conducting tissue locatedwithin the membranous portion of the ventricular septum. Bundle of Hisis surrounded by connective tissue from the central fibrous body 23,which constitutes an insulating layer to the chord-like bundle.Referring to FIGS. 1 and 2, the compact atrioventricular node 12 locatedin the right atrium 13 within the triangle of Koch 22 serves as thegateway of electrical conduction to the ventricles 6 and 11. Anatomictarget area 21 may be intended for stimulatory pacing electrodes makingcontact with (a) the penetrating Bundle of His and surrounding areas,which traverses through the membrane of septum, and (b) conductionelements of the triangle of Koch 22 and surrounding areas. This targetarea for electrodes implantation may be selected to allow controlledpacing of one or multiple myocardial structures.

At least some of the individual electrodes may be targeted forimplantation into the atrial tissues located in the vicinity of thetarget area 21. Activation of these electrodes may be used forconventional atrial pacing. The approach of implanting some electrodesinto the bundle of His while some other electrodes into the atrialtissues nearby may be advantageous for allowing cardiac pacing of boththe atrium (using atrial electrodes) and the one or both ventricles ofthe heart (using electrodes in the bundle of His)—all from the samesingle implantation procedure and using the same conduit for activationthereof.

FIGS. 3A, 3B, and 3C show perspective views of a distal tip of theconduit of the invention with multiple electrodes according to the firstembodiment thereof. Specifically, FIG. 3A shows the compressed assemblyof individual electrodes illustrated during the steps of delivery to theheart target area. The electrode assembly may include a tissueattachment spring/screw portion 31 designed to deliver spring/screw 33initially hidden inside the distal end of the conduit 32, as well as aplurality of pacing electrodes 34-39 located distally of the screw 33.Individual electrodes 34-39 may be made into a Z-shape and initiallycompressed and placed within the insulating outer sheath 40 with opening41 distally. The tissue attachment screw 33 may also be configured toserve itself as an electrode. The number of individual electrodes can be2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 electrodes. Eachindividual electrode or a group of individual electrodes may be equippedwith an individual wire connecting the respective electrode or a groupof electrodes to the pacing device on the other end of the singleconduit 31. In embodiments, effective and efficient delivery ofelectrical energy to the myocardium via the individual electrodes 34-39can be achieved by incorporation of steroid-elution into the individualelectrode tips 42 (electrode-tissue interface) that allows reliableheart pacing with low stimulation threshold.

Spaced proximally from the individual electrodes along the conduit 32there may be provided a ring electrode (not shown), which may be usedfor bipolar pacing purposes or individual electrode interrogationpurposes.

After placing the conduit 32 in the vicinity of the target area, thesheath 40 may be retracted backwards to reveal the distal end of theconduit 32, as shown by an arrow in FIG. 3B directed up. This allowsindividual electrodes 34-39 to be released to spring outwards and awayfrom the central axis of the lead 32 and spread radially around the lead32. At this stage, rotating the distal end of the lead 32 allowschanging the position of electrode tips if desired. Once the desiredorientation and position of individual electrodes is achieved, thedistal end of the lead 32 may be advanced forward to allow the tips 42of individual electrodes to penetrate into the cardiac tissue as seen inFIG. 3C. The screw 33 may be advanced forward from the inside cavity ofthe conduit 32 and rotated to secure the entire assembly of individualelectrodes to the cardiac tissue as shown by an arrow directed down.

Those skilled in the art will recognize that screw 33 can be shorterthan 5 mm and longer than 3 mm. Also, those skilled in the art willrecognize that individual electrodes 34-39 can cover the suitable targetarea with a diameter from about 5 mm to about 30 mm. In embodiments, thediameter of the circle formed by individual electrodes may be 5 mm, 10mm, 15 mm, 20 mm, 25 mm, 30 mm or any size in between.

Following evaluation of electrical functionality of individualelectrodes (described below in greater detail), the screw 33 may beretracted and the conduit 32 may be repositioned if needed until theproper function of at least some of the individual electrodes isachieved.

In embodiments, expanding individual electrodes released by retractingof the sheath 40 may form other geometrical figures in addition to acircle, for example they may form a line of dots representing individualelectrodes, a spiral of dots, and other arrangements as the invention isnot limited in this regard.

The material and design of the individual electrodes may follow aconvention established for these devices. A biocompatible wire withsuitable mechanical properties and electrical conductivity may be usedto form an individual electrode capable of being stored in a compressedstate inside the sheath 40 and when released spring outwards to adesired position for subsequent implantation into the cardiac tissue.

In yet further embodiments, some or all individual electrodes may bestacked along the conduit 32 along some length thereof so as to avoidcrowding of all electrodes together and occupying the entire availablecross-sectional area. In this case, the ends of electrodes 41 may bemade longer for those electrodes which are moved away from the distalend of the conduit 32 so as to assure a uniform height of all individualelectrodes upon release thereof from the sheath 40.

While in some embodiments, all individual electrodes 34-39 may befixedly assembled within the conduit 32, in other embodiments individualelectrodes may be organized together and placed within a lumen insidethe conduit 32 so as to allow one or several individual electrodes to beremoved after initial interrogation is complete.

FIG. 4 presents a perspective view of a distal end of a single conduitwith multiple electrodes according to the second embodiment of thepresent invention. Specifically, FIG. 4A shows the conduit assembly in acompressed state during delivery to the heart target area. The assemblyincludes a spring/screw tissue attachment portion 31 inside the conduit32, spring/screw 33 in this case located distal to a plurality ofmultiple pacing electrodes 34-39, and outer insulating sheath 43 withopening 41 distally. The number of individual pacing electrodes can be2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 electrodes. Afterretraction of the sheath 43, the conduit 32 is revealed, as shown by anarrow in FIG. 4B directed up, which in turn allows the electrodes 34-39to spread radially and away from the distal tip of the conduit 32.

FIG. 4C shows the step when the conduit 32 is moved closer to the spring33. After that, the spring 33, working optionally as an additionalelectrode or as a ground reference electrode, may be screwed into thetissue of target area and electrodes 34-39 may be advanced to penetratethe tissue of the target area as well. After the screw 33 enters thecardiac tissue, further manipulation (push forward and rotation) withthe distal portion of the electrode wires may be used to repositionelectrode tips to a more desired location.

FIG. 5 presents a perspective view of a tip of a conduit with multipleelectrodes according to the third embodiment of the present invention.More particularly, FIG. 5A shows the conduit assembly during thedelivery to the heart target area. The assembly includes a spring/screwtissue attachment portion 31 which may be retracted and retained insidethe distal portion of the conduit 60, spring/screw 33 extending from theportion 31, multiple pacing electrodes 55-58, and the outer insulatingretractable sheath 43. The electrodes 55-58 may be arranged along theperiphery of the conduit 60; every electrode may be placed in anindividual delivery slot, e.g. electrode 55 may be located inside theslot 61, electrode 58 may be positioned inside the slot 62 and so on.Each slot may contain an exit shaped to direct each respective electrodeon a trajectory diagonally outwards and away from the center of theconduit, for example using an enlargement 53 configured to deflect theelectrodes as they are moved along their respective slots. Inembodiments, the angle of direction for advancing each electrodediagonally outwards and away from the center may be from about 25degrees to about 70 degrees to the central axis of the single conduit.

After the distal end of the conduit 60 is delivered to the target area,the screw tissue attachment portion 31 may be advanced out of theconduit 60 and exposed to the cardiac tissue as shown by an arrow inFIG. 5B. Further, the screw/spring 33 may be screwed into the cardiactissue of target area. After that, individual electrodes 54-59 may beone by one or as a group (using a slider engaging some or all individualelectrodes—not shown) advanced forward and inserted into the cardiactissue of the target area.

One advantage of individual deployment of each electrode is that it maybe positioned at various desired depths so as to adapt the generallycircular pattern of electrodes to fit a particular geometry of thecardiac tissue for an individual patient. Another advantage of thisdesign is that those individual electrodes that may not be selected forfinal inclusion in the cardiac pacing of the patient may be withdrawnfrom the single conduit so as not to be present to remain in the cardiactissue in a passive role.

FIG. 6 presents a perspective view of a tip of a conduit with multipleelectrodes according to the fourth embodiment of the present invention.Specifically, FIG. 6A shows the conduit assembly as compressed andconfigured for the delivery to the heart target area. The assembly mayinclude a conduit 65, a movable portion 64 and multiple pacingelectrodes 67. At least some or all individual electrodes may contain atissue attachment spring/screw 68 at a distal tip thereof.

After delivery the lead tip to the target area for electrodeimplantation, the movable portion 64 may be retracted away from theconduit 65 as shown in FIG. 6B. The electrodes 67 may be configured tospring outwards and away from the center of the conduit, for examplewith the aid of a narrow neck 69 and enlarged conduit extension 70.Furthermore, one, several or every electrode 67 may be deliveredindividually and secured to the cardiac tissue of the target area bymoving it up/down and rotating thereof using individual electrode wires63 at the proximal end of the conduit of the invention.

FIG. 7 shows a schematic diagram of a leadless implantable pacemaker 71providing multiple electrodes. The pacemaker body 72 may be designed tocover multiple individual pacing electrodes 76 with tissue attachmentsprings at their respective ends/tips, wireless communicating microchip73, programmable processing microchip 74, single source of electricpower (battery) for energizing multiple electrodes 75 of the leadlesspacemaker 71, electrode multiplexer 78 and a signal amplifier 79. One,some or every electrode may contain a spring/screw 77 at its tip fortissue attachment. After the delivery the pacemaker to the target area,the electrodes may be activated and advanced to penetrate the tissue ofthe target area. In embodiments the number of electrodes may be 2, 3, 4,5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or24 electrodes. In further embodiments, the leadless pacemaker 71 mayhave individual electrodes arranged as individually-activated zones on asurface thereof, avoiding some or all of spring/screw altogether. Tissueattachment may be provided by the external shape of the pacemaker 71selected to provide adequate contact with the target cardiac tissue onceimplanted.

After implantation of the leadless pacemaker 71 to a target area ofcardiac tissue as described elsewhere in the specification, multipleindividual electrodes 75 may be interrogated to determine a subsetthereof meeting a predetermined acceptance criteria, after which theseselected active electrodes may be operated to provide electricalstimulation of multiple chambers of the heart from a single location,using a single pacemaker with a single battery to operate multipleactive electrodes 75.

In addition to providing a dedicated pacemaker to activate allelectrodes of the above described embodiments of the conduit of theinvention, it is contemplated that a multiplexer can be used to allowusing a conventional pacemaker with the conduit of the invention. FIG. 8shows a schematic diagram of a pacemaker of the present invention havinga single lead with multiple electrodes at the distal end thereof. Thepacemaker may comprise multiple electrodes 80 configured forimplantation into cardiac tissue of the target area, a single conduit 81for individual electrical connections with multiple electrodes 80, and amultiplexer 82 for communicating the multiple electrode connections tothe standard electrical inlet/outlet connections 83 of currentlyavailable pacemakers. The multiplexer may be configured to allowconnecting suitable electrodes to the pacemaker connections 83 at anappropriate time during the cardiac cycle. In one example, connectors 83may be connected by the multiplexer 82 to the individual electrodes 80selected for atrial pacing during the first part of the cardiac cycle.This may be used to provide a suitable P-wave stimulation to the atriaof the heart. At a later portion of the cardiac cycle, the multiplexer82 may be configured to connect other individual electrodes 80 to theconnections 83, this time activating those individual electrodes 80 thatare selected during the implantation procedure for stimulating the Hisbundle and cardiac ventricles with an electrical impulse generating aQRS complex.

In use, the single conduit of the present invention may be advancedthrough the blood vessels or subcutaneously towards the heart as in aconventional pacemaker implantation procedure. Once the distal end ofthe conduit is located in the vicinity of the target area, the outersheath may be retracted over the conduit (or another deploymentmechanism may be activated) so as to reveal multiple individualelectrodes. The electrodes may be then urged to spread away from thecenter of the distal end of the conduit to assume a predeterminedexpanded pattern.

After final positioning of the plurality of electrodes in the expandedpattern over the target cardiac tissue area, the conduit may be furtheradvanced forward and individual electrodes may be caused to be implantedinto the cardiac tissue. Using the conduit of the present invention, allindividual electrodes may be implanted at the same time or closelyfollowing each other—a key advantage in time savings and reduction inradiation exposure to the patient and the physician.

Individual electrodes at the proximal end of the conduit may then beconnected to a pacemaker programming device—individually, in groups, orvia a multiplexer. Following this implantation and electrical connectionprocedure, individual interrogation of each electrode or groups ofelectrodes may be commenced.

In embodiments, individual electrodes may be evaluated one by one or ingroups following a similar approach used for evaluating singleelectrodes in a traditional pacemaker implantation procedure. In oneexample, each individual electrode may be fully characterized byapplying cardiac pacing impulses at various voltages (typically in adescending pattern) in a unipolar or bipolar mode so as to determine aresponse from the heart. The heart response may be determined using forexample an ECG signal collected internally close to the heart and/orexternally using skin electrodes.

If positioned properly, an expanded pattern of electrodes may cover thetarget area including the triangle of Koch and the bundle of His as wellas surrounding atrial tissues. Collecting response signals frominterrogation of each individual electrodes may produce three familiesof responses—that of (i) pure atrial pacing, (ii) mixed signal pacing,and (iii) pure ventricular pacing resulting from stimulation of thebundle of His. Based on collected results, all individual electrodes maybe separated into those producing one of these three signal patterns andothers that may or may not be useful for pacing purposes. Within thesegroups of individual electrodes divided into groups based on theirrespective recorded responses, further separation may be attempted, forexample individual electrodes may be ranked based on the level ofminimally effective threshold—lower threshold electrodes may bepreferred for activation on a continuous basis so as to conserve theelectrical energy of the pacemaker and to extend the useful life of thepacemaker battery.

Acceptance for cardiac atrium pacing may be determined using a firstpredetermined acceptance criteria, for example appearance of anacceptable P-wave on the ECG tracing at the lowest stimulating voltage.Similarly, acceptance for cardiac ventricle pacing may be determinedusing a second predetermined acceptance criteria, for example appearanceof an acceptable QRS signal on the ECG tracing at the lowest stimulatingvoltage.

In embodiments, alternative acceptance criteria may be a confirmedselective or non-selective capture of the bundle of His as may bepreferred for pacing needs of a particular patient.

Depending on the nature of cardiac arrhythmia for a particular patientdefining a specific pacing need therefor, a final selection of the mostuseful electrodes may be conducted so as to assure a reliablestimulation arrangement for a particular patient.

As an alternative to a unipolar interrogation of each individualelectrode, a bipolar interrogation using an optional ring electrode or acentral screw electrode may be conducted if that offers any advantagefor a particular patient.

In further embodiments, individual electrodes may be paired so as toconduct interrogation of certain pairs of electrodes. In this case, ifthe total number of electrodes is not excessively high, all combinationsof pairs of electrodes may be evaluated. If however, there is a highnumber of electrodes present and conducting evaluation of each possiblecombination of electrodes is time consuming, additional selectionmethods may be deployed. In one example, a subset of acceptableindividual electrodes may be stratified further by each electrode firstundergoing a determination of the lowest voltage threshold for itsstimulating efficacy, followed by selecting of the top few electrodesthat exhibit the best stimulating pattern at the lowest voltage.Following such initial selection, these top selected electrodes may beevaluated in pairs to determine their best combination suitable forstimulating purposes for a particular patient.

In case none or only a few electrodes are exhibiting satisfactoryperformance, the conduit may be disconnected from the cardiac tissue andmoved to another location so as to implant the plurality of individualelectrodes at a better site in cardiac tissue. Following a repositioningof the electrodes, another round of testing as described above may becommenced to proceed until a suitable number and combination ofindividual electrodes may be found to satisfy pacing needs for apatient.

In further embodiments, as opposed to fully evaluating each individualelectrode by supplying a series of characterizing stimulating impulsesthereto and then moving to the next individual electrode, all electrodesmay be evaluated with the same initial characterizing impulse suppliedto individual electrodes one at a time. Following detection of responsefrom each individual electrode to the same initial impulse, a secondimpulse can be used to interrogate all electrodes followed by the thirdimpulse, fourth impulse etc. One advantage of this technique is that thefirst impulse may be selected to be at a low voltage, the second impulsemay be at a higher voltage, and subsequent impulses may be of yet higherpredetermined voltage levels. This approach may be advantageous whenincreasing the voltage of the circulating impulse so as to determinewhen at least one or a subset of the individual electrodes start toexhibit desired stimulating efficacy and a suitable response from theheart. Once that is achieved, further interrogation may be stopped—so asto conduct evaluation of all available electrodes in a shorter period oftime.

FIG. 9 shows a block diagram illustrating an exemplary sequence of stepsof the method of using the cardiac pacemaker of the invention. Themethod may include the steps of inserting multiple pacing electrodes ofthe single conduit into target heart zone (triangle of Koch and bundleof His), individually testing heart pacing effectiveness of everyindividual electrode inserted into the target heart zone using apredetermined acceptance criteria, selecting acceptable electrodes forfurther use as active electrodes, abandoning and optionally removing (atleast in some embodiments) rejected pacing electrodes from the hearttissue, optimizing pacing parameters such as intrinsic delays/phaseshifts for all accepted pacing electrodes, and adjusting the leadlength, position and slack before connection to multiplexer of apacemaker.

Example

The proof of concept was achieved in the animal experiment using an openchest porcine model. The prototype of a single conduit terminating witha plurality of individual electrodes was created using 6 Fr pacemakerelectrode with an extendable-retractable helix spring/screw tip and 4additional individual electrodes centered around the distal end of theconduit and electrically insulated from each other. The prototype wasimplanted in 4 adult animals on a beating heart through a small incisionin the right atrium and then secured by a purse-string suture tominimize blood loss. The prototype single conduit was manipulated insidethe heart, guided manually and assisted by straight and shaped styletspositioned in the inner lumen. Placement was further assisted byintracardiac electrogram recording. The prototype was placed into thearea of the triangle of Koch and successfully secured to the endocardiumvia an extendable spring/screw at the tip thereof. Electrograms wererecorded from all recording configurations. The presence of aventricular electrogram was confirmed in all configurations, thepresence of a bundle of His electrogram was confirmed in someconfigurations, and the presence of an atrial and His electrogram wasalso seen in some but not all of the recording configurations.

Subsequent testing demonstrated selective and nonselective His bundlecapture when pacing between one of the two individual electrodes (usedas a negative electrode) and the distal tip of the conduit (used as apositive electrode). Atrial capture was demonstrated between one of thefour individual electrodes and the distal tip of the conduit.Furthermore, atrial capture at low output (1 V) with His bundle captureat higher output (6V) was seen between one individual electrode and thedistal tip.

Additional pacing configurations in between the individual electrodesand between the individual electrodes and the ring electrodedemonstrated an ability to capture different areas of the heart andvariable capture thresholds. In further experiments, in addition tothese observations both selective and nonselective His bundle capturewas observed when pacing from different individual electrodes.

Examples of a bundle of His signal recording and pacing with differentchambers/tissues being captured from the same prototype electrodelocation are shown in FIGS. 10, 11, 12 and 13. After the animalsacrifice the prototype electrode fixation was confirmed by visualinspection and manual tug. The extendable-retractable spring/screw wasshown to be implanted in the triangle of Koch, which effectivelypositioned the individual electrodes around it in an area ofapproximately 1 cm in diameter.

FIG. 10 illustrates exemplary measurement of an HV interval in an animalheart. Generally, the HV interval defines the conduction time from thebundle of His to the first identifiable onset of ventricular activation.The HV interval may be measured at 34 ms, as seen in measurement 110 onthe second QRS complex. Shown on tracings 100, 101, 102, 103, 104 and105 are some of the recorded ECG leads signals, line 106 reflectsintracardiac recording from an electrode that is positioned near thebundle of His. Individual positions 107 (atrial electrogram), 108 (Hisbundle electrogram) and 109 (ventricular electrogram) are shown witharrows.

FIG. 11 illustrates selective exemplary stimulation of the bundle of Hisusing individual electrodes like those shown in FIG. 5 in an animalheart. Stimulation between the individual electrodes B3-B4 wasattempted. Tracing illustrates selective His bundle capture when pacingin this configuration. After stimulation was discontinued on A1electrode, the sinus rhythm tracing shows serial activation of the atria(corresponding to a P wave on the ECG tracing) followed by ventricles(corresponding to a QRS complex on the ECG tracing). Shown as tracings111, 112, 113, 114, 115, and 116 are some exemplary recordings of theECG leads signals, tracing 117 reflects intracardiac recording betweenthe electrodes B3-B4 that have been implanted into the triangle of Koch.Stimulus to QRS time 121 identical to the HV interval of 34 ms (see 110in FIG. 10) and narrow QRS may be used to confirm successful selectiveHis bundle capture using the individual electrodes as described above.Retrograde conduction to the atria is seen after the complexes with Hisbundle capture—as indicated by arrows 118, 119 and 120. This excludesdirect capture of the atria by the pacing stimulus.

FIG. 12 illustrates activation of the ventricular myocardium by bothselective and nonselective His bundle capture in the animal heart.Stimulation was conducted between the individual electrodes B2-B4.Tracings 122, 123, 124, 125, 126 and 127 are some of the ECG leadsignals, while tracing 128 reflects intracardiac recording from theprototype electrode that has been implanted into the triangle of Koch(between individual electrodes B2 and B4). Both selective (first 3 QRScomplexes) and nonselective His bundle capture (last 3 QRS complexes)are seen as the pacing output is decreased from 7 V to 5 V. NonselectiveHis bundle capture reflects some capture of the adjacent ventricularmyocardium as indicated by slight slurring of the initial QRS complexshown by arrow 129. Stimulus to QRS time during the selective Hiscapture is equal to HV interval shown in FIG. 10—confirming His bundlecapture. Retrograde conduction to the atria is seen in tracing 128 asindicated by arrow 130 (same as in FIG. 11). This excludes directcapture of the atria by the pacing stimulus.

Finally, FIG. 13 illustrates pacing of the atria by the prototypeelectrode implanted into the triangle of Koch of an animal heart.Prototype electrode is still fixed in the same position. Pacing isattempted between the individual electrodes B1 and B2. Atrial capture isseen in the first 2 complexes as indicated by a much longerstimulus-to-QRS time—137. Atrial capture by the pacing stimulus isfurther confirmed by the appearance of captured P waves in the first 2complexes on tracings 130, 131, 132, 133, 134 and 135. First 2 PQRScomplexes are paced, whereas the last 3 PQRS complexes are not and shownative conduction. Shown on tracings 130, 131, 132, 133, 134 and 135 arethe ECG leads signals, whereas tracing 136 reflects intracardiacrecording between the individual electrodes B1-B2 from the prototypethat has been implanted into the triangle of Koch in the same positionwhere His bundle capture was demonstrated from other electrode pairs(FIGS. 11-12).

It is contemplated that any embodiment discussed in this specificationcan be implemented with respect to any method of the invention, and viceversa. It will be also understood that particular embodiments describedherein are shown by way of illustration and not as limitations of theinvention. The principal features of this invention can be employed invarious embodiments without departing from the scope of the invention.Those skilled in the art will recognize, or be able to ascertain usingno more than routine experimentation, numerous equivalents to thespecific procedures described herein. Such equivalents are considered tobe within the scope of this invention and are covered by the claims.

All publications and patent applications mentioned in the specificationare indicative of the level of skill of those skilled in the art towhich this invention pertains. All publications and patent applicationsare herein incorporated by reference to the same extent as if eachindividual publication or patent application was specifically andindividually indicated to be incorporated by reference.

The use of the word “a” or “an” when used in conjunction with the term“comprising” in the claims and/or the specification may mean “one,” butit is also consistent with the meaning of “one or more,” “at least one,”and “one or more than one.” The use of the term “or” in the claims isused to mean “and/or” unless explicitly indicated to refer toalternatives only or the alternatives are mutually exclusive, althoughthe disclosure supports a definition that refers to only alternativesand “and/or.” Throughout this application, the term “about” is used toindicate that a value includes the inherent variation of error for thedevice, the method being employed to determine the value, or thevariation that exists among the study subjects.

As used in this specification and claim(s), the words “comprising” (andany form of comprising, such as “comprise” and “comprises”), “having”(and any form of having, such as “have” and “has”), “including” (and anyform of including, such as “includes” and “include”) or “containing”(and any form of containing, such as “contains” and “contain”) areinclusive or open-ended and do not exclude additional, unrecitedelements or method steps. In embodiments of any of the compositions andmethods provided herein, “comprising” may be replaced with “consistingessentially of” or “consisting of”. As used herein, the phrase“consisting essentially of” requires the specified integer(s) or stepsas well as those that do not materially affect the character or functionof the claimed invention. As used herein, the term “consisting” is usedto indicate the presence of the recited integer (e.g., a feature, anelement, a characteristic, a property, a method/process step or alimitation) or group of integers (e.g., feature(s), element(s),characteristic(s), propertie(s), method/process steps or limitation(s))only.

The term “or combinations thereof” as used herein refers to allpermutations and combinations of the listed items preceding the term.For example, “A, B, C, or combinations thereof” is intended to includeat least one of: A, B, C, AB, AC, BC, or ABC, and if order is importantin a particular context, also BA, CA, CB, CBA, BCA, ACB, BAC, or CAB.Continuing with this example, expressly included are combinations thatcontain repeats of one or more item or term, such as BB, AAA, Aft BBC,AAABCCCC, CBBAAA, CABABB, and so forth. The skilled artisan willunderstand that typically there is no limit on the number of items orterms in any combination, unless otherwise apparent from the context.

As used herein, words of approximation such as, without limitation,“about”, “substantial” or “substantially” refers to a condition thatwhen so modified is understood to not necessarily be absolute or perfectbut would be considered close enough to those of ordinary skill in theart to warrant designating the condition as being present. The extent towhich the description may vary will depend on how great a change can beinstituted and still have one of ordinary skilled in the art recognizethe modified feature as still having the required characteristics andcapabilities of the unmodified feature. In general, but subject to thepreceding discussion, a numerical value herein that is modified by aword of approximation such as “about” may vary from the stated value byat least ±1, 2, 3, 4, 5, 6, 7, 10, 12, 15, 20 or 25%.

All of the devices and/or methods disclosed and claimed herein can bemade and executed without undue experimentation in light of the presentdisclosure. While the devices and methods of this invention have beendescribed in terms of preferred embodiments, it will be apparent tothose of skill in the art that variations may be applied to the devicesand/or methods and in the steps or in the sequence of steps of themethod described herein without departing from the concept, spirit andscope of the invention. All such similar substitutes and modificationsapparent to those skilled in the art are deemed to be within the spirit,scope and concept of the invention as defined by the appended claims.

1-9. (canceled)
 10. A method of providing cardiac pacing comprising thesteps of: a. providing a flexible single conduit housing a plurality ofindividual wires extending therethrough and positioned alongside eachother at least in a portion of said single conduit, said plurality ofindividual wires terminating with a plurality of correspondingindividual electrodes located at a distal end of said single conduit, b.advancing said single conduit to position said distal end thereof near acardiac tissue target area while said plurality of individual electrodesare held in a collapsed position next to a center of said distal end ofsaid single conduit, c. expanding said plurality of individualelectrodes to an expanded position forming an expanded scattered patternof said plurality of individual electrodes about and away from saidcenter of said distal end of said single conduit, d. implanting saidindividual electrodes into said cardiac tissue target area while in saidexpanded scattered pattern, e. interrogating each individual electrodeof said plurality of individual electrodes to determine a subset of saidplurality of individual electrodes meeting a predetermined acceptancecriteria for capturing of and pacing the heart, and f. initiatingcardiac capture and pacing using at least some of individual electrodesof said subset of individual electrodes meeting said predeterminedacceptance criteria, said at least some individual electrode connectedvia corresponding individual wires of said single conduit to a pacemakerlocated outside the heart.
 11. The method as in claim 10, wherein saidcardiac tissue target area comprises triangle of Koch, bundle of His andsurrounding areas.
 12. The method as in claim 10, wherein saidpredetermined acceptance criteria in step (e) is appearance of anacceptable paced P-wave on an ECG tracing when said cardiac pacing isdesired to correct an atrial arrhythmia.
 13. The method as in claim 10,wherein said predetermined acceptance criteria in step (e) is selectivecapture of the bundle of His and/or triangle of Koch.
 14. The method asin claim 10, wherein said predetermined acceptance criteria in step (e)is nonselective capture of the bundle of His and/or triangle of Koch.15. The method as in claim 10, wherein said predetermined acceptancecriteria in step (e) is appearance of an acceptable QRS complex on anECG tracing when said cardiac pacing is desired to correctatrio-ventricular, atrial, or ventricular conduction disturbances. 16.The method as in claim 10, wherein in step (e) said subset of individualelectrodes is further stratified based on a lowest voltage of achievingsaid predetermined acceptance criteria.
 17. The method as in claim 10,wherein in step (f) remaining individual electrodes of said subset ofindividual electrodes are left in a passive state implanted in saidcardiac tissue.
 18. The method as in claim 17, wherein said step (f)further including a step of re-activation of said remaining individualelectrodes when a malfunction of the previously selected electrodes isdetected. 19-22. (canceled)